ObjectiveTo investigate the mechanism by which Notoginsenoside R1 （NGR1） ameliorates hypoxia/reoxygenation （H/R）-induced injury in AC16 human cardiomyocyte cell lines through the regulation of mitophagy. MethodsCommon genes linked to hypoxia/reoxygenation injury and mitophagy were identified by intersecting data from GeneCards and MitoCarta databases. AC16 cell viability was assessed via CCK-8 assay under varying NGR1 concentrations （0， 6.25， 12.5， 25， 50， 100， 200， 300， 400， 500 μmol/L）. AC16 cells were divided into the following groups： control group （Control）， model group （H/R）， and treatment groups （H/R + NGR1 at 100， 200 and 300 μmol/L）. Mitochondrial membrane potential （ΔΨm） was measured using 5，5'，6，6'-tetrachloro-1，1'，3，3'-tetraethylbenzimidazolylcarbocyanine iodide （JC-1） staining. Transcriptional levels of mitophagy-related genes （Parkin， Pink1， P62） were quantified by reverse transcription-quantitative PCR （RT-qPCR）. Protein expression of mitophagy-related markers （Parkin， Pink1， P62， and LC3BⅡ） was evaluated via Western blot analysis. Mitochondrial ultrastructure was visualized by transmission electron microscopy （TEM）. ResultsCompared to the control group， cell viability in the H/R group significantly decreased （P<0.01）. Treatment with NGR1 at concentrations above 100 μmol/L significantly enhanced the cell viability of AC16 cells compared to the H/R group （P<0.01）. H/R induced a significant decrease in mitochondrial membrane potential （P<0.01）， which was restored by NGR1 treatment （P<0.01）. The mRNA levels of Parkin， Pink1， and P62 in the H/R group were upregulated compared to the control group （P<0.05）， while NGR1 intervention downregulated their expression （P<0.05）. Protein expression levels of Parkin， Pink1， and LC3BⅡ in the H/R group significantly increased， while P62 expression decreased compared to the control group （P<0.01）. In contrast， different doses of NGR1 treatment significantly reduced the expression of Parkin， Pink1， and LC3BⅡ while increasing P62 expression （P<0.05）. TEM revealed that the mitochondrial structure in the H/R group was severely disrupted， with fragmented and disorganized cristae， which was alleviated by NGR1. ConclusionNGR1 ameliorates H/R-induced AC16 cell injury， and its mechanism may be associated with modulating the Pink1/Parkin pathway to suppress excessive mitophagy.

Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.

Objective:To investigate the effect of transforming growth factor beta 1 (TGF-β1) on the biological activity of infantile hemangioma (IH) -derived endothelial cells (HemECs) .Methods:Three proliferating IH tissues and three involuting IH tissues were collected from IH patients receiving surgical resection at the Department of Pediatric Surgery, West China Hospital, Sichuan University from February to August 2021. Primary HemECs were isolated from proliferating IH tissues, and human umbilical vein endothelial cells (HUVECs) served as the control. The TGF-β1 expression levels in tissues and cells were detected by immunohistochemical study and Western blot analysis. Cell counting kit-8 (CCK8) assay was performed to assess the effect of 0 (control group) - 100 ng/ml TGF-β1 on HemEC proliferation. HemECs were treated with 5 ng/ml TGF-β1 or without (control group), and after several hours of treatment, Transwell assay was performed to evaluate cell migration ability, and immunofluorescence assay to assess the changes in the expression of endothelial markers (platelet-endothelial cell adhesion molecule-1 [CD31], vascular endothelial cadherin [VE-cadherin]) and mesenchymal markers (α-smooth muscle actin [α-SMA], collagen type Ⅰ α 1 [COL1A1]). Comparisons between groups were conducted by t test or one-way analysis of variance. Results:Immunohistochemical study showed that proliferating IH tissues were stained positively for TGF-β1, which was expressed relatively abundantly; the percentages of TGF-β1-positive signal area were higher in the proliferating IH tissues (24.68% ± 3.74%) than in the involuting IH tissues (almost no expression). Western blot analysis revealed that the relative expression level of TGF-β1 was significantly higher in HemECs (1.08 ± 0.13) than in HUVECs (0.30 ± 0.04, t = 9.93, P < 0.001). CCK8 assay showed increased proliferative activity of HemECs in the 3.125-, 6.25-, 12.5-, 25-, 50- and 75-ng/ml TGF-β1 groups compared with the control group (all P < 0.05), and no significant difference was found between the 100-ng/ml TGF-β1 group and the control group ( P > 0.05). Transwell assay revealed an increased number of migratory HemECs in the 5-ng/ml TGF-β1 group (127 ± 6) compared with the control group (103 ± 9; t = 5.32, P < 0.01). Immunofluorescence assay showed significantly decreased fluorescence intensity of endothelial markers CD31 and VE-cadherin in the 5-ng/ml TGF-β1 group (5.441 ± 1.254, 5.073 ± 0.412, respectively) compared with the control group (9.518 ± 1.728,7.671 ± 0.921, t = 3.31, 4.46, P = 0.030, 0.011, respectively), and significantly increased fluorescence intensity of mesenchymal markers α-SMA and COL1A1 in the 5-ng/ml TGF-β1 group (8.074 ± 0.846, 5.885 ± 0.216, respectively) compared with the control group (0.393 ± 0.342, 0.295 ± 0.125, t = 14.58, 38.76, P < 0.001, < 0.000 1, respectively) . Conclusion:TGF-β1 was relatively highly expressed in the proliferating IH tissues and HemECs, and could promote the proliferation, migration and endothelial-to-mesenchymal transition of HemECs.

OBJECTIVE: To evaluate the effect and safety of Chinese medicine (CM) Fuzheng Huazhuo Decoction (FHD) in treating patients with coronavirus disease 2019 (COVID-19) who persistently tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: This retrospective cohort study was conducted at Shanghai New International Expo Center shelter hospital in China between April 1 and May 30, 2022. Patients diagnosed as COVID-19 with persistently positive SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) test results for ⩾8 days after diagnosis were enrolled. Patients in the control group received conventional Western medicine (WM) treatment, while those in the FHD group received conventional WM plus FHD for at least 3 days. The primary outcome was viral clearance time. Secondary outcomes included negative conversion rate within 14 days, length of hospital stay, cycle threshold (Ct) values of the open reading frame 1ab (ORF1ab) and nucleocapsid protein (N) genes, and incidence of new-onset symptoms during hospitalization. Adverse events (AEs) that occurred during the study period were recorded. RESULTS: A total of 1,765 eligible patients were enrolled in this study (546 in the FHD group and 1,219 in the control group). Compared with the control group, patients receiving FHD treatment showed shorter viral clearance time for nucleic acids [hazard ratio (HR): 1.500, 95% confidence interval (CI): 1.353-1.664, P<0.001] and hospital stays (HR: 1.371, 95% CI: 1.238-1.519, P<0.001), and a higher negative conversion rate within 14 days (96.2% vs. 82.6%, P<0.001). The incidence of new-onset symptoms was 59.5% in the FHD group, similar to 57.8% in the control group (P>0.05). The Ct values of ORF1ab and N genes increased more rapidly over time in the FHD group than those in the control group post-randomization (ORF1ab gene: β =0.436±0.053, P<0.001; N gene: β =0.415 ±0.053, P<0.001). The incidence of AEs in the FHD group was lower than that in the control group (24.2% vs. 35.4%, P<0.001). No serious AEs were observed. CONCLUSION FHD was effective and safe for patients with persistently positive SARS-CoV-2 PCR tests. (Registration No. ChiCTR2200063956).
Humans ; Drugs, Chinese Herbal/adverse effects* ; Retrospective Studies ; Male ; Female ; Middle Aged ; COVID-19 Drug Treatment ; SARS-CoV-2/drug effects* ; COVID-19/virology* ; Adult ; Aged ; Treatment Outcome

OBJECTIVE: To explore the therapeutic effects and underlying mechanisms of Dendrobium officinale (Tiepi Shihu) extract (DOE) on insomnia. METHODS: Forty-two male Sprague-Dawley rats were randomly divided into 6 groups (n=7 per group): normal control, model control, melatonin (MT, 40 mg/kg), and 3-dose DOE (0.25, 0.50, and 1.00 g/kg) groups. Rats were raised in a strong-light (10,000 LUX) and -noise (>80 db) environment (12 h/d) for 16 weeks to induce insomnia, and from week 10 to week 16, MT and DOE were correspondingly administered to rats. The behavior tests including sodium pentobarbital-induced sleep experiment, sucrose preference test, and autonomous activity test were used to evaluate changes in sleep and emotions of rats. The metabolic-related indicators such as blood pressure, blood viscosity, blood glucose, and uric acid in rats were measured. The pathological changes in the cornu ammonis 1 (CA1) region of rat brain were evaluated using hematoxylin and eosin staining and Nissl staining. Additionally, the sleep-related factors gamma-aminobutyric acid (GABA), glutamate (GA), 5-hydroxytryptamine (5-HT), and interleukin-6 (IL-6) were measured using enzyme linked immunosorbent assay. Finally, we screened potential sleep-improving receptors of DOE using polymerase chain reaction (PCR) array and validated the results with quantitative PCR and immunohistochemistry. RESULTS: DOE significantly improved rats' sleep and mood, increased the sodium pentobarbital-induced sleep time and sucrose preference index, and reduced autonomic activity times (P<0.05 or P<0.01). DOE also had a good effect on metabolic abnormalities, significantly reducing triglyceride, blood glucose, blood pressure, and blood viscosity indicators (P<0.05 or P<0.01). DOE significantly increased the GABA content in hippocampus and reduced the GA/GABA ratio and IL-6 level (P<0.05 or P<0.01). In addition, DOE improved the pathological changes such as the disorder of cell arrangement in the hippocampus and the decrease of Nissel bodies. Seven differential genes were screened by PCR array, and the GABA_A receptors (Gabra5, Gabra6, Gabrq) were selected for verification. The results showed that DOE could up-regulate their expressions (P<0.05 or P<0.01). CONCLUSION DOE demonstrated remarkable potential for improving insomnia, which may be through regulating GABA_A receptors expressions and GA/GABA ratio.
Animals ; Dendrobium/chemistry* ; Rats, Sprague-Dawley ; Male ; Sleep Initiation and Maintenance Disorders/blood* ; Plant Extracts/therapeutic use* ; Receptors, GABA-A/metabolism* ; Noise/adverse effects* ; Light/adverse effects* ; gamma-Aminobutyric Acid/metabolism* ; Sleep/drug effects* ; Rats ; Receptors, GABA/metabolism*

[Objective]To evaluate a third-generation applicator template for intracavitary combined with interstitial brachytherapy(IC-ISBT)suitable for locally advanced cervical cancer,aiming to improve therapeutic outcomes.[Methods]A retrospective study was conducted on patients with stage IB3-ⅣB cervical cancer treated at Sun Yat-sen University Cancer Center from January 2023 to October 2023.Magnetic resonance imaging data before and after external beam radiation therapy were collected and analyzed.According to the residual tumor after external beam radiation,high-risk clinical target volumes(HR-CTV)were delineated,based on which a third-generation IC-ISBT applicator template was designed.The dosimetric and therapeutic differences between using this applicator template(template implantation group)and traditional freehand interstitial implantation(freehand implantation group)were further compared.Statistical methods were used to analyze the data from both groups to test the efficacy and safety of the two approaches.[Results]The third-generation applicator template could accommodate different cervical structures and optimize needle path layout.The tumor volume in the template implantation group was significantly larger than in the freehand implantation group,showing statistical differences.In terms of dosimetric coverage(V100%),the template implantation group exhibited significant statistical differences compared with the freehand implantation group,demonstrating superior dose coverage.Additionally,the third-generation template showed advantages in protecting the rectum and sigmoid colon by potentially reducing high-dose points,while there were no significant differences in bladder dosimetry between the two methods.The primary cervical lesion remission rates were similar between the two groups.[Conclusion]The third-generation IC-ISBT applicator template is scientifically and rationally designed,especially for patients with larger tumor volumes and later stages.It is easy to operate,highly reproducible,and shows significant advantages in dose distribution and protection of surrounding critical organs.The template has the potential to be widely applied as a routine treatment option.

Objective To describe and analyze the current status,changing trend and influencing factors of the disease burden of cervical,endometrial and ovarian cancer in China from 1990 to 2021.Methods Data on incidence,mortality,disability-adjusted life year(DALY),and other indicators for cervical,endometrial and ovarian cancer were collected from the 2021 Global Burden of Disease database.Joinpoint regression models were used to analyze time trends,and age-period-cohort(APC)models assessed their impact on incidence and mortality.Spearman correlation analysis was performed to evaluate the relationship between the sociodemographic index(SDI)and the cancer indicators.Finally,the attributable risk factors for the disease burden were analyzed.Results From 1990 to 2021,age-standardized incidence rates of cervical and endometrial cancers in China significantly increased,while ovarian cancer showed no significant change.Age-standardized mortality,DALY,and years of life lost due to premature death(YLL)decreased significantly.The disease burden was heavier in middle-aged and older groups.APC model indicated an increase in cervical cancer incidence and a decrease in mortality over time.Furthermore,the incidence risks of cervical and endometrial cancers were elevated in successive birth cohorts,whereas a lower risk was observed for ovarian cancer.Correlation analysis showed significant associations between cancer incidence and mortality with SDI.Obesity has significantly contributed to the disease burden of common gynecologic cancers in China.Conclusion Mortality rates of cervical,endometrial and ovarian cancer have declined,while the incidence of cervical and endometrial cancers has significantly increased.The trends in incidence and mortality are influenced by age,period and cohort effects.Future efforts should focus on controlling risk factors like obesity to reduce the disease burden.

Objective To analyze the anatomical relationship between maxillary premolars and the alveolar bone and maxillary sinus using cone-beam computed tomography(CBCT),in order to provide an anatomical basis for immediate implant placement in maxillary premolars.Methods Data from 351 patients who underwent maxillary CBCT imaging at Yancheng Stomatological Hospital between January 2022 and December 2023 were collected.Measurements included the vertical distance between premolar roots and the maxillary sinus floor,intraosseous root length,angle between the tooth axis and alveolar bone axis,and buccal/palatal bone wall thickness,with comparisons of gender differences.Results The median vertical distance between single-rooted maxillary first premolars and the maxil-lary sinus floor was 10.16 mm,while that for second premolars was 4.61 mm.For double-rooted first premolars,the buccal root dis-tance was(4.13±3.99)mm and the palatal root was(5.14±3.94)mm.Maxillary first premolars were farther from the maxillary sinus floor than maxillary second premolars,with palatal roots farther than buccal roots.The intraosseous root length of maxillary first premo-lars was(9.20±1.44)mum,and maxillary second premolars(9.64±2.04)mm.Maxillary first premolars exhibited significantly shorter intraosseous root length than maxillary second premolars.The angle α between tooth axis and alveolar bone axis was 18.89°±6.33° for maxillary first premolars,and 12.65°±6.10° for maxillary second premolars,showing statistically significant differences.The buccal bone wall thickness of maxillary first premolars gradually decreased from 2 mm subcrest to the apex,while palatal bone walls of maxil-lary first premolars and both buccal/palatal walls of maxillary second premolars progressively thickened from 2 mm subcrest to the apex.Significant correlations were identified between angle α and buccopalatal bone wall thickness at mid-root and the apex:increased α cor-responded with reduced buccal wall thickness and enhanced palatal wall thickness.Conclusion The apical region of maxillary first premolars provides sufficient bone volume for primary stability in immediate implantation,though the thin buccal bone wall necessitates careful consideration of implant shape and positioning.Maxillary second premolar roots are closely adjacent to the maxillary sinus floor,requiring implant stabilization with the sinus floor cortical bone or me-siodistal walls of the extraction socket.